Implantable myocardial ischemia detection, indication and action technology

ABSTRACT

One embodiment enables detection of MI/I and emerging infarction in an implantable system. A plurality of devices may be used to gather and interpret data from within the heart, from the heart surface, and/or from the thoracic cavity. The apparatus may further alert the patient and/or communicate the condition to an external device or medical caregiver. Additionally, the implanted apparatus may initiate therapy of MI/I and emerging infarction.

This application is a divisional of U.S. application Ser. No.09/369,576, filed Aug. 6, 1999 now U.S. Pat. No. 6,501,983 which ishereby incorporated by reference in its entirety, and which claims thebenefit of U.S. Provisional Application No. 60/095,635, filed Aug. 7,1998, entitled “Method and Apparatus for In Vivo Detection of MyocardialIschemia.”

FIELD OF INVENTION

The present invention relates to methods and apparatus for detection andtreatment of the disease process known as myocardial ischemia and/orinfarction (MI/I).

BACKGROUND

Ischemia occurs when the blood supply to the heart muscle is temporarilyor permanently reduced, such as may result from the occlusion of acoronary artery. This occlusion may lead to local ischemia or infarctionof the heart muscle. Ischemia may also occur over large sections of theheart muscle due to conditions such as cardiac arrest, heart failure, ora variety of arrhythmias. The ischemic event can be of the so called“silent type” described in medical literature (e.g. not manifestingitself in terms of symptoms experience by the patient or obviousexternal indications). The event can also be chronic with continuouslyevolving symptoms and severity due to underlying heart disease, or veryabrupt and possibly even fatal due to infarction of large enough area ofthe heart to cause a large myocardial infarction.

The ischemic event often causes the performance of the heart to beimpaired and consequently manifests itself through changes in theelectrical (e.g. the electrocardiogram signal), functional (e.gpressure, flow, etc.) or metabolic (e.g. blood or tissue oxygen, pH,etc.) parameters of the cardiac function.

The conventional approach to detection of MI/I is to analyze theelectrocardiogram (ECG). An ischemic event results in changes in theelectrophysiological properties of the heart muscle that eventuallymanifest themselves as changes in the ECG signal. The current state ofthe art is to record these ECG signals from the body surface usingamplifiers and associated instrumentation. A standardized set ofelectrodes in an arrangement known as a 12-lead ECG has been developed.The conventional approach to the detection of ischemia and infarctionrelies on analysis and interpretation of characteristic features of theECG signal such as the ST-segment, the T-wave or the Q-wave.Computer-based technology has been employed to monitor, display, andsemi-automatically or automatically analyze the ischemic ECG changesdescribed above. The present technology includes ECG machines used indoctor's office, portable ECG machines known has Holter recorders,bedside monitors with displays, and sophisticated computer-based systemfor automatic analysis of the ECG signals.

Technology exists for providing therapy once ischemia is detected. Themost common approach involves thrombolytic therapy (by external infusionof drugs such as TPA or streptokinase) or opening of the blocked vesselsusing a variety of angioplasty catheter devices. In the event thatischemic condition results in malignant arrhythmia or arrest of theheart, an external defibrillator may be used to shock the heart andrestore the cardiac rhythm.

Technology also exists for implanting therapeutic devices for treatingelectrical conduction disturbances or arrhythmias of the heart. Thesedevices include implantable pacemakers, cardioverters and atrial andventricular defibrillators, drug infusion pumps as well as cardiacassist devices. The implantable devices typically use intracavitaryleads to sense the electrogram (EGM) and then provide electrical therapy(pacing or defibrillation) or mechanical therapy (pumping blood). Thesedevices sense the EGM and then utilize the features, such as improperconduction (in case of a pacemaker) or a fatal rhythm (in case of adefibrillator), or simply timing (to coordinate mechanical pumping).Notably, these devices do not specialize in the task of detecting,alerting the patient or treating ischemic heart disease.

Ischemia detection and analyses are usually done manually by the expertcardiologist or by computers employing algorithms to detectischemia-related changes in the ECG signals. The preferred features ofthe ischemia detecting computer algorithms are the ST-segment and theT-wave. These features show elevation, depression or inversion of theseECG signals associated with ischemia. The computer then carries out acareful measurement of the degree of elevation/depression in a specificlead. By identifying ischemia dependent changes from specific leads, theischemic event is attributed to a specific region of the heart.

The current approach to diagnosis is that after an ischemic event isperceived by the patient, they contact medical personnel such as the“911” system or their personal physician. Within the clinical setting,the patient is often monitored using a short recording of the ECG signalwhich may be interpreted by a physician. Alternately, the high riskpatient may be continuously monitored at the bedside in a cardiacintensive care unit. Therapy may include using drugs such as TPA, use ofcatheters for angioplasty (opening the blocked coronary vessel using aballoon or laser), or providing life support back up such asdefibrillation.

The aforementioned cardiovascular medical monitoring technology andmedical practice have several significant drawbacks in regard to thedetection and treatment of coronary ischemia which can result in severeconsequences to the patient up to and including death. They include thefollowing:

-   -   1) Not being able to immediately alert the patient and/or the        physician of an ischemic event, particularly a life threatening        event.    -   2) Not being ambulatory with the patient; and/or an inability to        provide continuous monitoring to the patient and indication of        the necessary diagnostic information to the physician.    -   3) Requiring input and interpretation of a physician or medical        practitioner when one may not be present.    -   4) Requiring monitoring devices external to the body, such as an        ECG monitor or external defibrillator, which are usually only        available in medical centers and hospitals, and which further        need special expertise and attention from medical personnel.    -   5) Reduced sensitivity or otherwise inability to detect ischemic        events due to loss of sensitivity from use of external        electrodes.    -   6) Loss of specificity as to the site of ischemia due to        inadequate placement of electrodes in the vicinity of the        ischemia or infarction.    -   7) Needing sophisticated expertise of a cardiologist to        interpret the clinical condition or needing monitoring        instruments with sophisticated computer-aided ECG signal        analysis capabilities.    -   8) Over reliance on use of ECG signals for detection and        inability to utilize and integrate other physiological data,        (e,g pressure, blood flow, and PO2).    -   9) Inability to immediately alert the patient or the physician        of the impending or emerging ischemic condition.    -   10) Inability to provide immediate treatment, particularly for        life-threatening events (e.g. myocardial infarction, cardiac        arrest).

SUMMARY OF THE INVENTION

Certain embodiments of the present invention relate to methods anddevices for detection of myocardial ischemia and/or infarction (MI/I).Preferred embodiments relate to electrodes and sensors, devices andmethods for interpreting ischemic conditions, devices and methods forinitiating the procedure to alert the patient and/or the care-giver, anddevices and methods for connecting with a device that provides therapy.MI/I may be detected using implantable devices and methods according tocertain embodiments of the present invention.

Embodiments may include a stand alone device or a modification ofanother implantable device such as a pacemaker, cardioverter,defibrillator, drug delivery pump or an assist device. Embodiments mayuse a variety of in vivo sensors located inside the human torso and/orinside the heart. The sensor device preferably includes electrodes thatare indwelling in the heart, on or in the vicinity of the heart, underthe skin, under the musculature, implanted in the thoracic or abdominalcavity. Preferably the sensor device also includes strategic placementof the electrodes to capture the EGM signal from various positions andorientations with respect to the heart. The sensor device alsopreferably includes other hemodynamic or mechanical sensors that aresensitive to the condition of the heart in MI/I. MI/I may be recognizedusing analysis of the features of the signal, namely the EGM, recordedby the electrodes and sensors. The features of the EGM signal (namely,depolarization and repolarization), morphology, and analyticalinformation such as the spectrum, wavelet transform, time-frequencydistribution and others, are utilized in the interpretation andrecognition of the MI/I condition. Separately or in conjunction, thehemodynamic (namely, blood pO2, pH, conductance, etc.) and mechanicalparameters (blood pressure, blood flow, etc.) are sensed according tothe embodiments of this invention. MI/I is then recognized byintegrating some or all of the sensor information. Embodiments maydetect this MI/I event and alert the patient using a variety of methods,including but not limited to vibration, electrical stimulation, auditoryfeedback, and telemetry. The device to alert the patient may in certainembodiments be incorporated within the instrument itself. The patientmay be alerted by direct communication via electrical, sound, vibrationor other means or indirect communication to an external device in anelectromagnetic link with the implanted device. Once the MI/I event isidentified, the device may also institute therapy, such as infusion of athrombolytic agent or delivering life saving shock in case of an arrest,semi-automatically or automatically. The therapy giving device may beintegrated with the MI/I detection, MI/I analysis, and/or patientalerting device into an integrated or separate stand alone system.

Embodiments of the invention may be used to detect MI/I from inside thebody as compared with the traditional approach of detection by placingelectrodes on the outer body surface of the torso. This is made feasiblein certain embodiments by using the MI/I detection technology in animplantable device. Embodiments utilize sensors, such as electrodes andleads, that record the EGM signal from inside the chest in the vicinityof the heart and/or from electrodes placed on the heart, and/or usingcatheters or leads placed inside the cavities (atria and ventricles).Embodiments may include built-in interfaces to electrodes, namelycircuits for amplification and filtering of the signals, and the circuitfor digitization (analog-to-digital conversion) and processing(microprocessor). Embodiments of the implantable device, using itsmicroprocessor, analyze the features of the EGM signal from these leadsto detect an ischemic event.

Embodiments also relate to the design, construction and placement ofelectrode sensors. Embodiments may include an electrode lead withmultiple sensors capable of recording EGM from multiple, strategiclocations in the chest or in and around the heart. This embodiment alsoincludes utilization of the body of the instrument and single ormultiple leads.

Embodiments also relate to detection of the ischemic event includingidentifying particular features of the EGM signal. These featuresinclude depolarization (i.e. initial excitation of the heart when a beatis initiated, coincident with the body surface QRS complex) andrepolarization (i.e. the subsequent repolarization of the heartcoincident with the body surface ST-segment and T-wave). MI/I results inalteration in depolarization and repolarization waves in selectedregions of the heart, for the case of focal ischemia, or the entireheart, for the case of global ischemia. These changes alter the actionpotential (of heart cells) as well as the conduction pattern (inselected regions or the whole heart). The alterations in actionpotential shape and conduction change together alter both thedepolarization features as well as the repolarization features).Depending on where an electrode is placed, these features may be seen indifferent recordings. The electrodes pick up the local signal (from theheart muscle in its vicinity) as well as the distal signal (distalmuscle areas as well as the whole heart). The characteristics of thissignal are identified in the form of shape changes, and these shapechanges can be identified in a variety of ways, including temporal,spectral, and combined approaches.

The MI/I detection technology according to embodiments of the presentinvention, may also utilize non-electrical measures, includinghemodynamic and mechanical parameters. An MI/I event may result in adegree of deprivation of oxygen to the heart muscle. This in turn mayresult in a decreased ability to perfuse the heart muscle as well as thebody. This may result in a cyclical reduction in the mechanicalperformance in terms of contractility and pumping action of the heart.Sensors placed inside the blood stream pick up the changes in bloodoxygen, pH, conductance, etc. resulting from the MI/I event. The MI/Ievent would lead to small changes in case of mild ischemia or infarct orsignificant changes in case of global ischemia or cardiac arrest. Thesensors are usually placed inside a catheter or a lead, although sometimes in the body of the instrument, and then measurements may be madevia the electronic circuit interfaces inside the implantable device. Themechanical function of the heart may be detected utilizing sensors andleads, including those for pressure, volume, movement, contractility,and flow.

Embodiments also relate to methods and devices for signaling the hostpatient or others (such as medical personnel) to the incidence of MI/I.When MI/I is detected, it is imperative to take therapeutic actionsrapidly and even immediately. Thus, the patient needs to be informed andthe caregiver physician needs to be informed. Embodiments of theinvention include devices and methods for communication between theimplantable device and the host/physician. One of these approaches is touse radio-frequency or radiotelemetry, while another is to communicatethrough electrical stimulation. Other approaches, including sound, andmagnetic fields are also devised. Embodiments may also utilize longdistance, remote and wireless means of communication using telephone,telemetry, Internet and other communication schemes. Embodiments mayalso include the code of communication by which the informationpertinent to MI/I is presented in detail. This code may be either analogor digital, relayed via the communication link, and then decoded by thereceiving instrument or individual. The code primarily signals to thehost patient, or the external device attached to the patient, ordirectly to the medical caregiver, the condition of MI/I. The code mayinclude information about EGM, the MI/I condition, and other relateddiagnostic information. The code may also include recommendation andinstructions to provide an immediate therapy to the patient to treatMI/I.

Another aspect of certain embodiments of the invention includes couplingof the MI/I detection technology to a variety of therapeutic devices.The implantable MI/I detection technology makes it feasible to rapidlyinitiate therapy through direct access to the body, circulatory systemor the heart. In some circumstances it is desirable to infuse drug suchas Streptokinase or TPA to treat the patient. Other drugs may also beinfused immediately or subsequently on a steady state basis. In otherinstances it is desirable to carry out procedures such as angioplasty.In case the MI/I event leads to a life-threatening arrhythmia or cardiacarrest, means to treat the arrhythmias to resuscitate the heart aredisclosed. These may include use of electrical pacing, cardioversionand/or defibrillation. In case the MI/I event leads to a failure of theheart, means to assist the heart are disclosed. These assistive devicesinclude left or right ventricular assistive device and artificial heartpump. Embodiments may declare interface of the implantable myocardialischemia detection technology to these therapeutic approaches and theuse of these therapies upon discovery of MI/I by the implanted devices.

Another aspect of certain embodiments of the invention includes the useof the technology in an implantable device. The implantable device mayinclude a hermetically sealed can, electronics, analog and digitallogic, microprocessor, power source, leads and sensors, circuits anddevices to alert the patient, communication link and interface to theexternal diagnostic and therapeutic means. Embodiments also includemodification of implantable arrhythmia detection devices, pacemakers,defibrillators, infusion pumps, or assist devices to have the novelfeatures described above. The technology used in embodiments of thepresent invention can be partially or fully integrated into theseinstruments. Embodiments further include hardware, software or firmwaremodification of the aforementioned devices to have MI/I detection,alerting and therapy initiating features.

BRIEF DESCRIPTION OF THE DRAWINGS

Certain embodiments of the invention are described with reference to theaccompanying drawings which, for illustrative purposes, are notnecessarily drawn to scale.

FIG. 1 illustrates a schematic illustration of the torso and heart whichalso includes the implantable device, its sensing lead, an alarm means,a therapy device, and a communication means to an external deviceaccording to an embodiment of the present invention.

FIG. 2: (a) illustrates a preferred embodiment including an implanteddevice such as a pacemaker with a full 12-lead electrocardiographicconfiguration (L, R, F and V1 through V6, and ground reference) using animplantable intra-cavitary and intrathoracic lead; (b) illustrates asecond preferred embodiment using an implanted device and a singlesuitably positioned intrathoracic lead with multiple sensors in thechest and the ventricular cavity of the heart; and (c) illustrates athird preferred embodiment with a suitably placed device with multipleelectrical contact sensors on the implanted device can and a suitablythreaded lead through the thoracic, abdominal and the ventricular cavityalong with the sensor means.

FIG. 3 illustrates a preferred embodiment, such as acardioverter-defibrillator with suitable sensing or shocking lead withsensor means indwelling the heart and ventricular cavity and a series ofsensors on the shocking lead on the epicardium or the thoracic,abdominal and ventricular cavity.

FIG. 4 illustrates three of the many placements and shapes of theimplanted device inside the thoracic or abdominal cavity, and the sensormeans on each can of the implanted device with each sensor insulatedfrom the can (see the inset), according to embodiments of the presentinvention.

FIG. 5 illustrates three preferred embodiments with suitable implanteddevice in the thoracic cavity, placement of different electrode leadsand sensors and their different configurations with respect to theheart. The sensor configuration includes leads with (a) unipolar, (b)bipolar sensing and (c) physiologic sensor means inside the ventricularcavity of the heart.

FIG. 6 illustrates the (a) electronics and microprocessor system used inthe implantable myocardial ischemia detection device, and (b) thecircuit diagram for amplification and filtering of the EGM signal,according to embodiments of the present invention.

FIG. 7 illustrates (a) the depolarization and repolarization signals ofthe electrocardiogram, the action potential, normal and ischemic EGM,the pressure signals, and time-frequency response characteristics of theEGM; and (b & c) the electrical activation pattern on the heart asvisualized by isochronal conduction distribution in (b) normallyconducting zones and (c) ischemic zones.

FIG. 8( a) illustrates various communication links between theimplantable device and the external monitoring devices, includingalerting the subject with the aide of a loud speaker, vibrator orelectrical stimulation, communication to and external device via RFcommunication, audio communication, and magnetic field modulationaccording to embodiments of the present invention.

FIG. 8( b) illustrates the implantable MI/I detection technologypiggy-backed or incorporated as a part of a modified implantablepacemaker or a cardioverter-defibrillator according to embodiments ofthe present invention.

DETAILED DESCRIPTION

Certain embodiments of the invention pertain to methods and devices fordetecting ischemia or infarction, diagnosing, alerting the patientand/or treating the ischemic heart disease.

Implantable myocardial ischemia and/or infarction (MI/I) detectiontechnology according to certain preferred embodiments is illustrated inFIG. 1. Embodiments include methods and devices to detect and treatMI/I. One embodiment of a method includes: i) placement/implantation ofthe device inside the chest or other body cavity, ii) placement andimplantation of electrodes and sensors to selected areas of themyocardium, iii) connection of one or more of the electrodes and sensorsto the implanted device, iv) detection of an ischemic event by theanalysis of the EGM signal and sensor data, v) the method of analysis ofthe EGM signal using signal processing means in time and frequencydomain, vi) communicating the stored EGM signals to an external deviceusing telecommunication means, vii) alerting the patient of the event,vi) communication with the medical attendant using telecommunicationmeans, and vii) initiating or implementing medical therapy for MI/I.Embodiments may include some or all of the above elements, which aredescribed in more detail below.

One preferred embodiment is illustrated in FIG. 1. It includes aplurality of devices (101) and sensors (102) that are implanted in thehuman body (103). Referring to FIG. 1, this implementation may includeone or more of the following steps: i) a device that would reside insidethe body (103) and alert the patient (106) or the medical attendant ofan impending or ongoing ischemic event and undertake therapeutic action,ii) one or more implanted sensors (102) positioned in selected areas ofthe heart (104), such as a ventricular cavity (105), and connected tothe aforementioned device, iii) detecting an ischemic event, iv)alerting the patient of the event as depicted in (106), v)communication, as depicted in (107) with a device external to the body(108) or a medical attendant, vi) administration of medical therapy viaan intracavitary pacing electrode (109), infusion of drug through thebody of the lead (102) or shocking the heart between leads (102 and110).

Another preferred embodiment of the device and its method of use isillustrated by FIG. 2( a). The device (101) is implanted in the thoraciccavity under the skin or muscle in the vicinity of the heart (104). Thesensing may be accomplished by a detailed electrocardiographic systemthat provides a device for biopotential recording from locations aroundthe heart that result in a more complete assessment of the ischemicregions of the heart. The leads are positioned in one or moreconfigurations within the chest to form an internal Einthoven's triangle(an external Einthoven's triangle is a concept known in the art). Thisconfiguration provides the advantage of enhanced signal sensitivity fordiscrete selectable areas of the myocardium and allows for easydetermination of particular cardiac vectors. The resultant 12-leadelectrocardiographic system is employed by those skilled in the art on(not internal to) the chest to provide projection of the cardiac dipoleat various electric field orientations. A cardiologist or a computerprogram is then employed to determine the site and degree of MI/I byinterpretation of the electrocardiogram. In the present invention, anintra-thoracic lead system is designed to record the EGM activity usinga plurality of sensors situated to record projections of the cardiacdipole from inside the body in a manner analogous to the Einthoven'striangle and a 12-lead recording system from outside the chest. A lead(201) system comprises a biocompatible insulated carrier device with aplurality of electrically conducting metallic sensors that conduct theEGM signal from in or around the chest to the circuitry within theimplanted device. The lead depicted in FIG. 2 carries three sensors(202, 203, 204) corresponding respectively to the left arm (L), theright arm (R) and the foot (F) projections of the 12-lead system. AWilson's central terminal, a central terminal derived through aresistive network, is provided to derive the leads I, II, III and thethree augmented leads (external, but not internal, Wilson's centralterminal and leads are concepts known to the art). The lead is attachedto the body of the implanted, hermetically sealed device (101) via aconnector (205) that provides a feed-through interface to the circuitrywithin. Another lead (206) carries additional sensors (207 through 212)corresponding respectively to the V1 through V6 projections of the12-lead electrocardiographic system. The body of the device or aconducting sensor incorporated there in provides the ground or thecircuit common reference G (213). The sensor signals are electricallyconnected via the lead to the circuitry within the implanted device. TheEGM signals recorded from this lead system is analyzed for the featuresof MI/I.

Another preferred embodiment shown in FIG. 2.2( b) comprises animplanted device (221) in the abdominal or lower thoracic cavity (220)with a preferred lead system (222) with a plurality of sensors. The leadsystem (222) makes a connection through a feed-through connector (223)to the circuitry of the implanted device (221). The lead (222) issuitably implanted within the thoracic cavity and in and around theheart (105) to place the sensors at locations that allow recordingsanalogous to the aforementioned 12-lead electrocardiographic system. Thedesign involves the placement of the conducting sensors so that theirplacement inside the thoracic areas of the body (103) and in and aroundthe heart (104,105) preferably corresponds to the 12-leadelectrocardiographic system. Thus, the sensors V1 through V6 and L, R,and F (224) along with the ground reference G on the body of the device(225) represents all the electrodes needed to reconstruct the fullelectrocardiographic system, comprising leads I, II, III, augmentedleads, and chest leads, suitable for implantable technology. The EGMsignals from this lead system (222) may then be analyzed for theindications of MI/I.

Another embodiment is depicted in FIG. 2( c). An implanted device (230)is located in the lower thoracic or abdominal cavity and a lead (231)with sensors therein is threaded through the intra-thoracic areas of thebody (103) and in and around the heart (104,105). The lead carries thesensors L, R and F, while the body of the implanted device carries thesensors V1 through V6, wherein the sensor array shown as (232). The bodyof the device (230) carries the ground or the circuit common G, whilethe conductive sensor elements shown as the open circles are insulatedfrom the body of the device as shown by the dark rings around thecircular sensor body (233). This lead system suitably captures the EGMsignals from the various regions of the body which are then electricallyconducted by the lead (231) to the implanted device (230).

Still another embodiment is illustrated in FIG. 3. An implanted device(101) placed inside the body (103), utilizes a plurality of leads (301)and (306) and sensors therein. The lead (301) carries with it thesensors L, R and F for EGM sensing within and around the heart (104,105). The lead 301 also carries plurality of sensors (302) formechanical or hemodynamic information from within the ventricular cavity(105). The lead (306) connects sensor element (307) carrying pluralityof sensor V1 through V6 (308). The body of the device (101) carries theground reference G.

In yet another embodiment of the present invention, an implanted deviceis placed inside the chest in the proximity to the heart. The device isshaped in a manner so that it can carry on its case one or more leads(electrodes and their combination) suitable for recording multiple EGMsignals. There are several locations that are preferred. FIG. 4 showsthe thoracic part of the body (103), the heart (104), and three of thesuggested locations and shapes of the device (401, 402, 403), each oneof these locations and electrode placements is to be used independentlyand exclusively. These locations allow preferred orientation of theelectrodes and leads for detection of EGM signal. For example, location(401) with three electrodes (405, 406, 407) give preferred orientationof the ECG in conventional left arm and lead I between (405, 406) signalfrom the cardiac dipole. The three sensors also give other projectionsfrom the heart when taken in pairs (406, 407) and (405, 407). The bodyof the can or an additional metal sensor insulated from the can is usedas a ground reference. Alternately, the signals from the sensors (405,406, 407) may be summed using resistive network, known, in externaldevices but not implanted devices, as Wilson's central terminal, toprovide a common or reference signal. The location (403) analogously has3 electrodes (408, 409, 410) which give the conventional right arm andlead I between (408, 409) signal, and other differential pairs II andIII between (409, 410) and (408, 410). The location (403) has sensors V1through V6 (411) giving 6 chest lead signals. In all these designs andplacements the sensors are mounted on the encasement of the device knownas the can and hence do not require separate leads or wires going outfrom the can via the feed-through to the heart or to the body. The canand the associated sensors can be entirely hermetically sealed andcontained in a single case. The can may be made of a biocompatiblematerial including, but not limited to stainless steel, titanium or abiocompatible engineered polymer such as polysulfone or polycarbonateand the like. The inset in FIG. 4 shows the electrical sensor element(406) surrounded by insulating ring (407) mounted on the can (403). Theconducting sensor element provides electrical connection to thecircuitry inside the can of the implanted device. The electrical sensoror the body of the implanted device serves as the ground or the circuitcommon reference. While three preferred embodiments are illustrated, theexact location of the implanted device and the electrical sensorelements can be varied to provide sensing and the lead oriented toimprove the sensitivity to detection of the MI/I from a particularregion of the heart. For example, a can at location (401) would pick upleft and superior infarcts, a can at location (402) would pick up rightand superior infarct, and a can at location (403) would pick up left orright inferior infarcts. In addition, in certain embodiments thecontainer or can may be eliminated or integrated into one of the othercomponents.

In a preferred embodiment of the device, an intracavitary indwellinglead system, as depicted in FIG. 5, is used to sense the EGM signals.Referring to FIG. 5( a), the implanted device (101) encases in the canthe electronics while the body of the can serves as the ground or thereference G or otherwise a sensor on the lead serves as the ground orthe reference (501). The intracavitary lead consists of a lead (502)going from the device (101) into the right ventricular cavity via thevenous blood vessel by the methods well known in the art. The lead (502)may be preferentially threaded through the right or the left subclavianveins. The lead (502) may also be threaded through inferior vena cava orIVC. The lead (502) is placed in the atrial or the ventricular cavity orboth. The lead (502) also may lodge in the SVC and through the septalregion in the left ventricular cavity. The lead (502) may be placed inthe left ventricle via the arterial vessel. The lead made ofbiocompatible material including, but not limited to polyurethane orsilicon carries within it the metallic coil or wire for proper insertionof the lead (502). The lead (502) carries at its tip the pacingelectrode (503) by which electrical stimulation is delivered to theheart muscle. Although depicted in this figure as being in contact withthe ventricular muscle, the pacing electrode (503) may also be incontacting with atrial muscle or other suitable pacing regions on theheart surface. The sensing and the pacing electrodes may be designedinto a single lead body or separate lead bodies. The atrial andventricular chambers of the heart may be sensed and paced separately orjointly. The external body of the lead also carries the conductingsensor element such as (504) to contact and capture electrical signalfrom the cavity of the heart (105). A plurality of electricallyconducting contact points (505) on the lead serve as sensor elements. Asthese sensor elements (504) span the atrium to the ventricle, typicallyon the right side of the heart, these sensor elements (504) capture theEGM signal associated with that part of the heart. In the preferredembodiment in FIG. 5( a), the sensor elements are arranged in theunipolar configuration wherein the sensor elements are well separatedfrom one another, each capable of capturing electrical signal withrespect to the ground reference G on the body of the can or electrode(501). In another preferred embodiment illustrated in FIG. 5( b), thesensor elements are arranged in a bipolar configuration wherein pairs ofsensor elements (506, 507) are closely spaced. A plurality of sensorelement pairs (508) are arranged in the region spanning the atrium,ventricle or both. In another preferred embodiment, illustrated in FIG.5( c), the sensor element can be at or close the tip of the catheter(510) and may include one or more of many hemodynamic sensors (e.g.pressure, pO2, pH, temperature, conductivity, etc.) or mechanicalsensors (strain gauge, accelerometer, etc.).

Preferably the implanted device consists of a casing or a can made ofbiocompatible and hermetically sealed case consistent with long termimplantation in the hostile environment of the body (with its warmtemperature, humidity, blood, etc.). The can is shaped in a variety offorms illustrated in FIG. 2 and FIG. 3. The circuitry associated withthe sensor is housed inside this can and may be driven by battery power,typically one of the many contemporary pacemaker/defibrillator batteriesusing lithium or lithium ion or polymer battery technology well known inthe art. The internal circuitry may utilize ultra-low power analog anddigital circuit components built from miniaturized packages and runningoff the battery power supply. One overall schematic design isillustrated in FIG. 6( a) and consists of the input protection stage(601) which serves to protect the amplifier from possible shock hazards.This front-end should also meet electrical safety and leakagespecifications conforming to safety standards as set by AAMI, AmericanHeart Association and other standard setting bodies. This stage isfollowed by the amplifier (602) and followed by electrical isolationcircuitry (603), if necessary. Isolation can be electrical or optical.The isolation circuit is followed by the output stage (604) which feedsall the analog signals from multiple channels into a multiplexer, MUX(605). The multiplexed signal is digitized using an A/D converter(analog to digital converter) (606) and then fed into a microprocessor(607). The principal circuit component is the EGM amplifier, which isdesigned using operational amplifiers as illustrated in FIG. 6( b). Theamplifier circuitry consists of protection (610) and filtering (611)components (including diodes, capacitors and inductive chokes),operational amplifier based instrumentation amplifier (612), and activecircuit filters for band-pass filtering (613). In various embodiments,the hardware implementation may use a low power, low voltagemicroprocessor or a custom-designed ASIC or a fully custom VLSI circuit.In an alternative embodiment, the hardware would be contained, orotherwise piggy-backed onto an implantable pacemaker orcardioverter-defibrillator. In this case the ischemia detectiontechnology would use information derived from the existing leads of theimplanted pacemaker or defibrillator. Also, the detection software wouldbe embedded in the RAM or the ROM and executed by the microprocessor ofthe implanted pacemaker or cardioverter-defibrillator.

The sensors of the implanted device are preferably configured to capturethe EGM signal and other physiologic data. From these signals and data,algorithms implemented by the microprocessor and its software identifythe ischemic event. Embodiments utilize the EGM signals from inside thebody using a plurality of sensors placed inside the thorax and in andaround the heart. The sensors preferably seek to mimic the internal orimplanted form of the Einthoven triangle and the 12 leadelectrocardiographic system. The complete 12 lead system may not alwaysbe used and the MI/I event can be captured from only a limited set ofleads and electrodes. The complete or partial set of these sensors, soarranged, provide a projected view of the heart's dipole at varioussensor locations. The signals recorded from a sensor then give anindication of the MI/I event in its vicinity and the recorded pattern isindicative of the degree of severity of the MI/I event. Certainembodiments utilize both depolarization and repolarization signalcomponents of the EGM signal to detect ischemia events. As illustratedin FIG. 7, ECG signal (701) is accompanied by the action potentialsignal (702), the EGM signal (703) and the pressure signal (704). UnderMI/I conditions, these respective signals may be modified as shown in(705, 706, 707 and 708). Note the appearance of notches in the QRScomplex and depression of the ST-segment (705 and 710). Correspondingly,the action potential (706) shows change in upstroke (713), duration andshape (714). Consequently, the EGM signal shows fractionation andmultiple depolarization and changed shape (707). The ventricularpressure signal shows a reduction in magnitude as well as shape change(708). The ischemic conditions are some times localized to parts of theheart (focal ischemia or infarct) and at other times throughout theheart (global). Ischemia results in slowed conduction and possiblefractionation of the conduction patterns. FIGS. 7( b) and 7(c)illustrate the conduction on the heart (750), with FIG. 7( b)illustrating the conduction in normal conditions, with traces (752)showing isochronal lines t1 through t6 (places receiving simultaneousactivation). An infarcted is indicated as a region 751 on the heart withno isochronal lines, and consequently it is a region which alters theconduction pattern. Therefore, under ischemic conditions, as illustratedin FIG. 7( c), the conduction pattern (752) is altered as indicated bythe isochrones t1 through t10. The isochrones show different pathways,indicating dispersion and fractionation of conduction. This dispersionand fractionation of conduction produces the EGM signal depicted forischemic hearts (707) and its features thereof (716).

The EGM signal for normal versus ischemic myocardial tissue can bedistinguished using a variety of means including waveform analysis donein both the temporal and frequency domain and combination of both, whichis called a time-frequency method. FIG. 7( a) graphically illustratesthe EGM signal for a healthy heart (703) with a relatively large majorpeak and related inflection and transition points corresponding todepolarization and repolorization events occurring during the cardiaccycle (702). In contrast, the ischemic signal shown in (707) showssignificantly more peaks and has unusual transitional points (716). Thisphenomenon is known as fragmentation and is readily distinguishable. Analternate approach is to detect ischemia in the frequency domain. FIG. 7also illustrates the time-frequency analysis of the EGM signal. The EGMsignal is analyzed through Fourier analysis which is well known in theart and its frequency components are thus obtained. Since the EGM signalis time-varying, time-frequency analysis is more suitable so as toobtain instantaneous frequencies at different times in the cardiaccycle. Magnitude of signal power, indicated by horizontal lines atvarious frequencies (717) and plotted versus time (718) is calculated.In this case, the ischemic EGM time-frequency distribution (719) isdistinguished from the time-frequency distribution of the healthy EGMwaveform (720) by a broader range of frequencies at one or moredepolarization, repolarization and fractionation event locations.Further during repolarization, there is shift towards lower frequenciescorresponding to the ST-segment elevation or depression and T-wavemorphology changes in the ECG. Several different approaches oftime-frequency and time-scale analyses are applicable to calculatinglocalized frequency information at various instants of the EGM signals.Normal and ischemic EGM waveforms/signals are thus distinguished and theelectrodes or sensors displaying the characteristic changes identifyischemia in their vicinity. This approach is extended to analysis ofsignals from various sensors. FIG. 7( a) shows the cavitary pressuresignal in normal (704) and ischemic (707) hearts. Analogously, acavitary probe measuring conductance can obtain an estimate of theventricular volume by methods well known in the art. The magnitude andmorphology of the conductance signal is also indicative of MI/I.Analogously, ventricular volume signal assessed by the aforementionedconductance method also identifies local changes in the conductance andproportionately the volume in the region of the ventricular cavity.Therefore, a comparison of such signals placed in different positions inthe heart (e.g. 505, 508, 509), allows estimation of ventricular volumesat different points in the cardiac cycle and at different locations inheart. Information from the EGM signals (electrical conduction) andhemodynamic/mechanical signals (conductance, pressure, ventricularvolume, blood volume, velocity etc.), may be used separately or combinedby one or more algorithms, programmable devices or modified pacemaker,cardioverter, defibrillator systems seeking to detect an ischemic event.Ischemic diagnostic function may be further enhanced by combininganalysis of ECG and hemodymanic data with metabolic/chemical data (e.g.PO2, CO2, pH, CK (creatine kinase)) collected using in dwelling sensorswhich may be chemical FETs, optical fibers or otherwise polarimetric oroptical based, and the like, all well known in the art.

In another embodiment of the ischemia detection sensors, a use is madeof the multiple sensors spanning the lead in the ventricular cavity. Thesensors (505 or 508 or 509) in FIG. 5 capture the changes in the EGMsignals in their vicinity. An analysis of the relative morphologieswould help identify the ischemia in the vicinity of the electrode. Theelectrode sensors record the EGM signals whose morphology or frequencycharacteristics in normal or MI/I conditions is similarly analyzed bythe methods illustrated in FIG. 7( a). The EGM signal recorded andanalyzed results from spontaneous heart beats or from paced beats.Spontaneous heart beats are produced by the heart's own natural rhythm.Paced beats are produced by a pacing electrode usually at the tip of thelead placed in the atrial or the ventricular cavity. The morphology andthe frequency characteristics of the paced beats are analyzed for MI/Icondition.

Once an incident of MI/I is detected, the patient or the medical caregiver needs to be informed so that quick intervention may be taken.Noting that certain aspects of embodiments relate to an implanteddevice, the device needs to communicate the signal out to the patientand/or the physician. FIG. 1 provided a scheme for the communicationbetween the implanted device (101) and the subject (103) or the externaldevice (108). Now, for further detail, FIG. 8 illustrates an implanteddevice (801) comprising its amplifier and data-acquisition system (802)and microprocessor (803) communicates data and message to the subject orthe external device via a D/A converter (804), a parallel port (805), aserial port (806 or 807). The D/A converter is connected to an amplifier(808) which drives a loud speaker, buzzer or a vibrator (811). Theexternal device may receive this information via a microphone (815). Thesubject may preferably receive the alert message via audio or vibratorysignal (811). Alternately, the subject may receive the indication of anMI/I via an electrical stimulus feedback delivered via a voltage tocurrent converter, V-I (829) delivered to the case of the implanteddevice or to a stimulating lead. The serial port communicates theelectrical signals via a modem (809), and a transmitter (812) to anantenna (815) for radio frequency or audio telemetry to the externaldevice. The external device receives the radio telemetry communicationvia an antenna (816) and a receiver (817) and subsequently conveys thesedata to a computer connected to the receiver. Alternately, the implanteddevice may use a serial port (807), connected to a modem (810) and atransmitting coil capable of generating and receiving magnetic fields(818). By pulsed or alternating magnetic field, a message pertaining tothe MI/I event or digitized data from the microprocessor (803) arerelayed to the external device. An external coil capable of generatingor receiving magnetic field communicates the message to and from theimplanted device (819) via magnetic induction. The magnetic fieldfluctuations are processed and a message or data stream may becommunicated to a computer connected to the external device. These areamong many alternative means to enable communication between theimplanted device and the external device may be operated/worn by thephysician or the patient. Other communication technologies well known inthe art may also be utilized. The implanted and the external deviceengage in a unidirectional (sending the MI/I alert or sending actualdigital or analog data over the link) or bidirectional (external devicesending commands, internal sending the data, for example).

Certain embodiments also include devices and methods for taking atherapeutic action. The therapeutic action is possible because implanteddevice provides an early indication of an event of MI/I. Therefore,there may be adequate time for this system to perform therapeuticactions to prevent or minimize the development of an infarction. Invarious embodiments of the invention, therapeutic actions may comprise:infusion of thrombolytic agents such as TPA and streptokinase oranticoagulant agents such as heparin. Since it is known that there istreatment window of several hours after infarction which can preventmore serious medical complications, a timely bolus or steady release ofthese medicines may prevent or otherwise ameliorate the conditions thatmay be precipitating the MI/I. FIG. 8( b) illustrates the schema inwhich the implanted device (801) equipped with a lead (833) connected toa sensing means (831) initiates the action of transmitting a message viaa transmitter (832) in a manner described previously. It also initiatesinfusion of any of the aforementioned drugs via an infusion line or acatheter (835). For example, the drug may be in the catheter tip itselfembedded in a slow release polymeric matrix whose release is actuated bythe implanted device. Alternately, the drug may be in the device itselfand released via infusion tubing (835). The acute MI/I may precipitate alife-threatening arrhythmia. In case such an event, involvingarrhythmias such as ventricular tachycardia or fibrillation, theimplanted device may initiate electrical rescue therapy, such as pacing,cardioversion or defibrillation. An electrical shock may be given viatwo leads, which may be a combination of the can of the implanted device(801) and an intracavitary lead (833) or a combination of subcutaneousor an epicardial or intrathoracic lead (834) and an intracavitary lead.Thus, the implanted device would initiate the therapeutic proceduressemi-automatically by first alerting the patient or automatically viainfusion of a drug or delivery of electrical rescue shock.

While aspects of the present invention have been described withreference to the aforementioned applications, this description ofvarious embodiments and methods shall not be construed in a limitingsense. The aforementioned is presented for purposes of illustration anddescription. It shall be understood that all aspects of the inventionare not limited to the specific depictions, configurations or relativeproportions set forth herein which may depend upon a variety ofconditions and variables. The specification is not intended to beexhaustive or to limit the invention to the precise forms disclosedherein. Various modifications and changes in form and detail of theparticular embodiments of the disclosed invention, as well as othervariations of the invention, will be apparent to a person skilled in theart upon reference to the present disclosure. For example, the logic toperform various analyses as discussed above and recited in the claimsmay be implemented using a variety of techniques and devices, includingsoftware under microprocessor control or embedded in microcode, orimplemented using hard wired logic.

While the invention described above presents some of the preferredembodiments, it is to be understood that the invention in not limited tothe disclosed embodiment but rather covers various modifications andequivalent arrangements included within the spirit and scope of theappended claims.

1. A method for monitoring electrogram signals in a subject, comprising:acquiring electrogram signals within the subject by positioning aplurality of sensors transveneously within the subject, the electrogramsignals including a depolariztion wave region and a repolarization waveregion, the sensors electrically coupled to an implanted deviceincluding electronics therein; analyzing the depolarization wave regionof the electrogram signals using the implanted device to obtaininformation relating to changes in the depolarization wave region; anddetermining whether MI/I has occurred, using the information relating tochanges in the depolarization wave region.
 2. A method as in claim 1,further comprising analyzing the repolarization wave region of theelectrogram signals using the implanted device to obtain additionalinformation relating to changes in the repolarization wave region, andwherein the determining whether MI/I has occurred also includes usingthe additional information related to changes in the repolarization waveregion.
 3. A method for monitoring electrogram signals in a subject,comprising: acquiring electrogram signals from the subject's heart, theelectrogram signals including a depolariztion wave region and arepolarization wave region; analyzing the depolarization wave region ofthe electrogram signals using electronics positioned within the subject,wherein the analyzing includes obtaining depolarization informationrelating to changes in the depolarization wave region due to MI/I;analyzing the repolarization wave region of the electrogram signalsusing the electronics positioned within the subject, wherein theanalyzing includes obtaining repolarization information relating tochanges in the repolarization wave region due to MI/I; and determining,in the subject, whether MI/I has occurred, using the depolarizationinformation and the repolarization information.
 4. A method of detectingmyocardial ischemia in a subject, comprising analyzing an electrogramsignal by determining its temporal features synchronous to the Q, R, S,and T waves in a surface ECG signal, wherein determining its temporalfeatures synchronous to the Q, R, S, and T waves includes providing aplurality of sensors adapted to deliver signals to a device implanted inthe subject, storing an electrogram signal from each lead into a digitalmemory in the device, and comparing an acquired electrogram signal tothe stored electrogram signal.
 5. A method as in claim 4, wherein theanalyzing includes: identifying changes in the morphology ofdepolarization upstroke synchronous with the Q and R waves; identifyingchanges in the morphology of depolarization downstroke synchronous withthe R and S waves; and identifying changes in the morphology ofrepolarization synchronous with the S and T waves.
 6. A method as inclaim 5, further comprising obtaining the electrogram signal from atleast one lead positioned in a location selected from the groupconsisting of endocardial, epicardial, thoracic cavity, subpectorial andsubcutaneous.
 7. A method as in claim 6, wherein the analyzing comprisesanalyzing a unipolar electrogram signal.
 8. A method as in claim 6,wherein the analyzing comprises analyzing a bipolar electrogram signal.9. A method for distinguishing normal and ischemic signal informationcomprising: analyzing signals derived from a plurality of sensorsimplanted transveneously in a subject, the sensors adapted to obtainsignals comprising a waveform of at least one heartbeat, the waveformincluding a depolarization region and a repolarization region; whereinthe analyzing signals comprises analyzing the waveform using at leastone method selected from the group consisting of a temporal domainmethod and a frequency domain method, wherein the temporal domain methodcomprises determining a magnitude of a signal power over thedepolarization region and repolarization region of at least oneheartbeat; and wherein the frequency domain method comprises performinga spectral analysis of a frequency component of the waveform over thedepolarization region and the repolarization region of at least oneheartbeat.
 10. A method as in claim 9, wherein the plurality of sensorsare selected from one or more of the group consisting of pressuresensors, volume sensors, conductance sensors, impedance sensors, pHsensors, pO₂ sensors, temperature sensors, and blood-based biochemicalsensors.
 11. A method as in claim 9, wherein the analyzing signalscomprises analyzing the waveform using a temporal domain method.
 12. Amethod as in claim 9, wherein the analyzing signals comprises analyzingthe waveform using a frequency domain method.
 13. A method as in claim9, wherein the analyzing signals comprises analyzing the waveform usinga temporal domain method and a frequency domain method.
 14. A method formonitoring a subject for MI/I, wherein a pacemaker is connected to thesubject's heart, the method comprising: acquiring a paced electrogramsignal within the subject, the paced electrogram signal including adepolarization wave region and a repolarization wave region; obtaininginformation relating to changes in the depolarization wave region over aplurality of heartbeats; obtaining additional information relating tochanges in the repolarization wave region over a plurality ofheartbeats; and analyzing the information relating to changes in thedepolarization wave region and the additional information relating tochanges in the repolarization wave region using electronics positionedin the subject and determining whether MI/I has occurred.
 15. A methodfor treating a subject comprising: implanting a device in the subject;acquiring electrogram signals within the subject using the device, theelectrogram signals including a depolariztion wave region and arepolarization wave region; determining whether MI/I has occurred in thesubject using the device in the subject, wherein the determining whetherMI/I has occurred includes one of: (i) analyzing the depolarization waveregion of the electrogram signals, wherein the analyzing includesobtaining depolarization information relating to changes in thedepolarization wave region due to MI/I, or (ii) analyzing thedepolarization wave region and the repolarization wave region of theelectrogram signals, wherein the analyzing includes obtainingdepolarization and repolarization information relating to changes in thedepolarization and repolarization wave regions; generating a therapysignal in the device when a determination that MI/I has occurred ismade; and initiating a therapy in the subject based on the therapysignal generated by the device.
 16. A method as in claim 15, wherein thetherapy comprises delivering at least one drug selected from the groupconsisting of bicarbonate, epinephrine, heparin, TPA, streptokinase, andbeta blockers.
 17. A method as in claim 15, wherein the at least onedrug comprises an anti-arrhythmic drug.
 18. A method as in claim 15,wherein the device includes at least one drug embedded in a polymermatrix and initiating therapy includes the release of the drug throughthe polymer matrix.
 19. A method as in claim 15, wherein the deviceincludes at least one drug embedded in a portion of the device selectedfrom a lead, a catheter and tubing, and initiating therapy includesreleasing a drug from the portion of the device.
 20. A method as inclaim 15, wherein initiating the therapy includes delivering anelectrical shock to the subject.
 21. A method as in claim 20, whereinthe device includes a plurality of leads and positioning the leads atone or more positions selected from the group of intracavitary,epicardial, thoracic, and subcutaneous positions in the subject andtherapy includes delivering a shock to the subject through at least oneof the leads.
 22. A method as in claim 15, wherein the therapy isinitiated immediately after detecting MI/I.
 23. A method as in claim 15,wherein the therapy includes treatment that can be carried out by theimplanted device.
 24. A method as in claim 23, wherein the treatmentthat can be carried out by the implanted device is initiated immediatelyafter detecting MI/I.
 25. A method as in claim 23, wherein the treatmentthat can be carried out by the implanted device is initiated within onehour after detecting MI/I.
 26. A method as in claim 15, whereindetecting MI/I comprises detecting MI/I selected from the groupconsisting of transient MI/I, permanent MI/I, and recurrent MI/I.
 27. Amethod as in claim 15, wherein detecting MI/I comprises detecting MI/Ifollowing an event selected from the group consisting of cardiac arrest,cardioversion, and defibrillation.
 28. A method as in claim 15, whereindetecting MI/I comprises detecting MI/I following an event selected fromthe group consisting of drug infusion and angioplasty therapy.
 29. Amethod as in claim 15, wherein detecting MI/I comprises detecting MI/Iin the presence of an event selected from the group of arrhythmia andnormal sinus rhythm.
 30. A method as in claim 15, further comprisinggenerating an alarm signal when a determination that MI/I has occurredis made, and transmitting the alarm signal to a position external to thedevice.
 31. An apparatus for determining the location of a MI/I event ina subject, comprising an implantable device including a plurality ofsensors adapted to be positioned in and around the heart, the devicefurther including means for analyzing the changes in electrogram signalsreceived from the sensors and means for determining the location usingdipole projection.